Maternal pregravid body mass index and child hospital admissions in the first 5 years of life: results from an Australian birth cohort.

OBJECTIVES: To examine the association of maternal pregravid body mass index (BMI) and child offspring, all-cause hospitalisations in the first 5 years of life. METHODS: Prospective birth cohort study. From 2006 to 2011, 2779 pregnant women (2807 children) were enrolled in the Environments for Healthy Living: Griffith birth cohort study in South-East Queensland, Australia. Hospital delivery record and self-report baseline survey of maternal, household and demographic factors during pregnancy were linked to the Queensland Hospital Admitted Patients Data Collection from 1 November 2006 to 30 June 2012, for child admissions. Maternal pregravid BMI was classified as underweight (<18.5 kg m(-)(2)), normal weight (18.5-24.9 kg m(-)(2)), overweight (25.0-29.9 kg m(-)(2)) or obese (⩾30 kg m(-)(2)). Main outcomes were the total number of child hospital admissions and ICD-10-AM diagnostic groupings in the first 5 years of life. Negative binomial regression models were calculated, adjusting for follow-up duration, demographic and health factors. The cohort comprised 8397.9 person years (PYs) follow-up. RESULTS: Children of mothers who were classified as obese had an increased risk of all-cause hospital admissions in the first 5 years of life than the children of mothers with a normal BMI (adjusted rate ratio (RR) =1.48, 95% confidence interval 1.10-1.98). Conditions of the nervous system, infections, metabolic conditions, perinatal conditions, injuries and respiratory conditions were excessive, in both absolute and relative terms, for children of obese mothers, with RRs ranging from 1.3-4.0 (PYs adjusted). Children of mothers who were underweight were 1.8 times more likely to sustain an injury or poisoning than children of normal-weight mothers (PYs adjusted). CONCLUSION: RESULTS suggest that if the intergenerational impact of maternal obesity (and similarly issues related to underweight) could be addressed, a significant reduction in child health care use, costs and public health burden would be likely.

Community Opioid Dispensing after Injury (CODI): Cohort characteristics and opioid dispensing patterns.

BACKGROUND: Despite a focus of opioid-related research internationally, there is limited understanding of long-term opioid use in adults following injury. We analysed data from the 'Community Opioid Dispensing after Injury' data linkage study. AIMS: This paper aims to describe the baseline characteristics of the injured cohort and report opioid dispensing patterns following injury-related hospitalisations. METHODS: Retrospective cohort study of adults hospitalised after injury (ICD-10AM: S00-S99, T00-T75) in Queensland, Australia between 1 January 2014 and 31 December 2015, prior to implementation of opioid stewardship programs. Data were person-linked between hospitalisation, community opioid dispensing and mortality collections. Data were extracted for 90-days prior to the index hospital admission, to establish opiate naivety, to 720 days after discharge. Median daily oral morphine equivalents (i.e., dose) were averaged for each 30-day interval. Cumulative duration of dispensing and dose were compared by demographic and clinical characteristics, stratified by drug dependency status. RESULTS: Of the 129,684 injured adults, 61.3 % had no opioids dispensed in the 2-year follow-up period. Adults having any opioids dispensed in the community (38.7 %) were more likely older, female, to have fracture injuries and injuries with a higher severity, compared to those with no opioids dispensed. Longer durations and higher doses of opioids were seen for those with pre-injury opioid use, more hospital readmissions and repeat surgeries, as well as those who died in the 2-year follow-up period. Median dispensing duration was 24-days with a median daily end dose of 13 oral morphine equivalents. If dispensing occurred prior to the injury, duration increased 10-fold and oral morphine equivalents doubled. Adults with a documented dependency prior to, or after, the injury had significantly longer durations of use and higher doses than the rest of the cohort receiving opioids. Approximately 7 % of the total cohort continued to be dispensed opioids at 2-years post injury. CONCLUSION: This is a novel population-level profile of opioid dispensing patterns following injury-related hospitalisation, described for the time period prior to the implementation of opioid stewardship programs and regulatory changes in Queensland. Detailed understanding of this pre-implementation period is critical for evaluating the impact of these changes moving forward.

A brief history of botulism in South Africa.

When looking back into the history of botulism and contemplating the final understanding of the syndrome and the ultimate solutions, there are four facets that stand out clearly. The first is that much of the solution was guided by astute observations, curious travellers, committed veterinarians and particularly farmers themselves who were able to relate the occurrence of the condition to climatic and grazing conditions. Secondly, there was the identification of the osteophagia and pica syndrome which led to the feeding of bone-meal as a successful mitigating measure as well as the establishment that botulism was not due to a plant poisoning. Thirdly, the solution of the problem depended on the integration of experience and knowledge from diverse disciplines such as soil science, animal behaviour and husbandry, nutrition, botany and ultimately advanced bacteriology and the science of immunology. Finally it required the technical advancement to produce toxoids in large quantities and formulate effective aluminium hydroxide precipitated and oil emulsion vaccines.

Activation of hypoxic response in human embryonic stem cell-derived embryoid bodies.

Oxygen tension can provide an important determinant for differentiation and development of many cells and tissues. Genetic regulation of hemato-endothelial commitment is known to respond to oxygen deprivation via stimulation of hypoxia inducible factors (HIFs). Here, we use a closed bioreactor system to monitor and control the dissolved oxygen during differentiation of human embryonic stem cells (hESCs) via formation of embryoid bodies (hEBs). Exposing hESC-derived EBs to ambient oxygen at or below 5% results in stabilization of HIF-1alpha and increased transcription of hypoxic responsive genes. Interestingly, we find that rather than HIF-1alpha expression being stable over prolonged (7-16 days) culture in hypoxic conditions, HIF-1alpha expression peaks after approximately 48 hours of hypoxic exposure, and then declines to near undetectable levels, despite constant hypoxic exposure. This transient stabilization of HIF-1alpha during hESC-derived EB culture is demonstrated for four distinct stages of differentiation. Furthermore, we demonstrate hEB cell expansion is slowed by hypoxic exposure, with increased apoptosis. However, hEB cell proliferation returns to normal rates upon return to normoxic conditions. Therefore, although hypoxia effectively stimulates hypoxic responsive genes, this single variable was not sufficient to improve development of hemato-endothelial cells from hESCs.

Ten-year outcomes following traumatic brain injury: a population-based cohort.

PRIMARY OBJECTIVE: To quantify the 10 year health service use (HSU) and mortality outcomes for people with a traumatic brain injury (TBI). RESEARCH DESIGN: A population-based matched cohort study using linked administrative data from Manitoba, Canada (Manitoba Injury Outcome Study). METHODS AND PROCEDURES: An inception cohort (1988-1991) of hospitalized cases with TBI aged 18-64 years (n = 1290) was identified and matched to a non-injured comparison group (n = 1290). Survival analysis, Negative binomial and Poisson regression were used to quantify associations between injury and HSU/mortality outcomes for 10 years following the TBI event. MAIN OUTCOME AND RESULTS: The majority of deaths (47.2%) occurred in the first 60 days following injury. Excluding the first 60 days, the adjusted 10 year mortality remained elevated (mortality rate ratio = 1.48, 95% CI = 1.02-2.15). After adjusting for demographic characteristics and pre-existing health status, the TBI cohort had more post-injury hospitalizations (rate ratio (RR) = 1.54, 95% CI = 1.39-1.71), greater cumulative lengths of stay (RR = 5.14, 95% CI = 3.29-8.02) and a greater post-injury physician claims rate (RR = 1.44, 95% CI = 1.35-1.53) than the non-injured cohort. CONCLUSIONS: People who sustain a TBI and survive the initial acute phase of care experience substantially increased long-term morbidity compared to the general population, regardless of the level of injury severity.

Long-term mortality following injury in working-age adults: a systematic review.

Priorities for prevention activities and planning for services depend on comprehensive knowledge of the distribution of the injury-related burden in the community. The aim of this systematic review was to quantify the effect of being injured, compared with not being injured, on long-term mortality in working age adults. Cohort studies were selected that were population-based, measured mortality post-discharge from inpatient treatment, included a non-injured comparison group and related to working-age adults. Data synthesis was in tabular and text form with a meta-analysis not being possible because of the heterogeneity between studies. Eleven studies met the inclusion criteria. All studies found an overall positive association between injury and increased mortality. While the greatest excess mortality was evident during the initial period post-injury, increased mortality was shown in some studies to persist for up to 40 years after injury. Due to the limited number of injury types studied and heterogeneity between studies, there is insufficient published evidence on which to calculate population estimates of long-term mortality, where injury is a component cause. The review does suggest there is considerable excess mortality following injury that is not accounted for in current methods of quantifying injury burden, and is not used to assess quality and effectiveness of trauma care.

Hot tea and tiny tots don't mix: A cross-sectional survey on hot beverage scalds.

OBJECTIVE: Hot beverage scalds are a leading cause of burns in young children. The aim of this study was to look at the circumstances surrounding these injuries in terms of setting, mechanism, supervision and first aid to inform a prevention campaign. METHODS: A cross-sectional study was delivered via iPad to parents and caregivers presenting with a child aged 0-36 months with a hot beverage scald at a major paediatric burns centre. RESULTS: Of the 101 children aged 0-36 months that presented with a hot beverage scald over a 12-month period, 54 participants were included. The scald aetiology was as expected with the peak prevalence in children aged 6-24 months, pulling a cup of hot liquid down over themselves. The majority of injuries occurred in the child's home and were witnessed by the caregiver or parent. The supervising adult was often in close proximity when the scald occurred. Less than a third (28%) of participants received recommended first aid treatment at the scene, with an additional 18% receiving this treatment with three hours of the injury-usually at an emergency department. CONCLUSIONS: While the aetiology of these scalds were as expected, the low use of recommended burn first aid was of concern. Although supervision was present in almost all cases, with the parent/caregiver close-by, this proximity still permitted injury. Attentiveness and continuity of supervision, which can be difficult with competing parental demands, appear to play a more important role role; as do considerations of other safety mechanisms such as hazard reduction through keeping hot drinks out of reach and engineering factors such as improved cup design. By incorporating the findings from this study and other research into a hot beverage scald prevention campaign, we hope to see a change in knowledge and behaviour in parents and caregivers of young children, and ultimately a reduction in the incidence of hot beverage scalds.

Long term health outcomes after injury in working age adults: a systematic review.

BACKGROUND: Estimating the contribution of non-fatal injury outcomes remains a considerable challenge and is one of the most difficult components of burden of disease analysis. The aim of this systematic review was to quantify the effect of being injured compared with not being injured on morbidity and health service use (HSU) in working age adults. METHODS: Studies were selected that were population based, had long term health outcomes measured, included a non-injured comparison group, and related to working age adults. Meta-analysis was not attempted because of the heterogeneity between studies. RESULTS: Nine studies met the inclusion criteria. In general, studies found an overall positive association between injury and increased HSU, exceeding that of the general population, which in some studies persisted for up to 50 years after injury. Disease outcome studies after injury were less consistent, with null findings reported. CONCLUSION: Because of the limited injury types studied and heterogeneity between study outcome measures and follow up, there is insufficient published evidence on which to calculate population estimates of long term morbidity, where injury is a component cause. However, the review does suggest injured people have an increased risk of long term HSU that is not accounted for in current methods of quantifying injury burden.

Linking biosensor responses to Cd, Cu and Zn partitioning in soils.

Soils bind heavy metals according to fundamental physico-chemical parameters. Bioassays, using bacterial biosensors, were performed in pore waters extracted from 19 contrasting soils individually amended with Cd, Cu and Zn concentrations related to the EU Sewage Sludge Directive. The biosensors were responsive to pore waters extracted from Zn amended soils but less so to those of Cu and showed no toxicity to pore water Cd at these environmentally relevant amended concentrations. Across the range of soils, the solid-solution heavy metal partitioning coefficient (K(d)) decreased (p<0.01) with increasing amendments of Cu and Zn; Cu exhibited the highest K(d) values. Gompertz functions of Cu and Zn, K(d) values against luminescence explained the relationship between heavy metals and biosensors. Consequently, biosensors provide a link between biologically defined hazard assessments of metals and standard soil-metal physico-chemical parameters for determining critical metal loadings in soils.

Microbial indicators of heavy metal contamination in urban and rural soils.

Urban soils and especially their microbiology have been a neglected area of study. In this paper, we report on microbial properties of urban soils compared to rural soils of similar lithogenic origin in the vicinity of Aberdeen city. Significant differences in basal respiration rates, microbial biomass and ecophysiological parameters were found in urban soils compared to rural soils. Analysis of community level physiological profiles (CLPP) of micro-organisms showed they consumed C sources faster in urban soils to maintain the same level activity as those in rural soils. Cu, Pb, Zn and Ni were the principal elements that had accumulated in urban soils compared with their rural counterparts with Pb being the most significant metal to distinguish urban soils from rural soils. Sequential extraction showed the final residue after extraction was normally the highest proportion except for Pb, for which the hydroxylamine-hydrochloride extractable Pb was the largest part. Acetic acid extractable fraction of Cd, Cu, Ni, Pb and Zn were higher in urban soils and aqua regia extractable fraction were lower suggesting an elevated availability of heavy metals in urban soils. Correlation analyses between different microbial indicators (basal respiration, biomass-C, and sole C source tests) and heavy metal fractions indicated that basal respiration was negatively correlated with soil Cd, Cu, Ni and Zn inputs while soil microbial biomass was only significantly correlated with Pb. However, both exchangeable and iron- and manganese-bound Ni fractions were mostly responsible for shift of the soil microbial community level physiological profiles (sole C source tests). These data suggest soil microbial indicators can be useful indicators of pollutant heavy metal stress on the health of urban soils.

Cool Runnings - an app-based intervention for reducing hot drink scalds: study protocol for a randomised controlled trial.

BACKGROUND: Globally, burns are the fifth leading cause of non-fatal children's injuries, and the leading cause of childhood burns is hot beverage scalds. Although there have been a number of programmes aimed at preventing scalds in children, very few have specifically addressed hot beverage scalds, and fewer have reported a reduction in injury rates. In Australia, hot beverage scalds account for 18 % of all childhood burns - a figure that has remained constant for the past decade. Innovative new technologies, such as Smartphone applications (apps), present a novel way for delivering individual-level injury prevention messages. The low cost, scalability and broad reach make this technology an ideal channel for health interventions. One of the latest methods being used in health-related apps aimed at behaviour change is gamification. Gamification uses the gaming principles of rewards, competition and personalisation to engage participants and motivate them towards preferred behaviours. This intervention will use a Smartphone app-based platform that combines gamification and behaviour-change strategies to increase knowledge and awareness of hot beverage scald risks and burn first aid among mothers of young children. METHODS/DESIGN: This is a two-group, parallel, single-blinded randomised control trial (RCT) to evaluate the efficacy of a Smartphone app-based injury prevention intervention. The primary outcome measure is change in knowledge. Change in knowledge is measured in three components: knowledge of correct burns first aid; knowledge of the main cause of burns/scalds in children aged 0-15yrs; knowledge of the main age group at risk for burns/scalds. The secondary outcome measures relate to the gamification methods, measuring participants frequency of engagement with the Cool Runnings app. Queensland-based mothers aged 18+ years who own a Smartphone and have at least one child aged 5-12 months are eligible to participate. DISCUSSION: To our knowledge, this is the first study to evaluate an app-based delivery of injury prevention messages, and the first study to test the efficacy of gamification techniques in an injury prevention intervention. If this intervention is found to be effective, this RCT will provide a platform for targeting other childhood injury prevention campaigns. TRIAL REGISTRATION: This trial was registered on 14 January 2016 with the Australian New Zealand Clinical Trials Registry ( ACTRN12616000019404 ).

Inaccurate, inadequate and inconsistent: A content analysis of burn first aid information online.

OBJECTIVE: With the popularity of the Internet as a primary source of health-related information, the aim of this website content analysis was to assess the accuracy and quality of burn first aid information available on the Internet. METHODS: Using the search term 'burn first aid' in four popular search engines, the first 10 websites from each search engine were recorded. From a total of 40 websites recorded, 14 websites were evaluated after removing duplicates. Websites were assessed on content accuracy by four independent reviewers with checks conducted on inter-rater reliability. Website quality was recorded based on Health on the Net Code of Conduct (HONcode) principles. RESULTS: Country of origin for the 14 websites was the US (7), Australia (6), and New Zealand (1). The mean content accuracy score was 5.6 out of 10. The mean website quality score was 6.6 out of 12. Australasian websites scored lower for quality but higher for accuracy. The US websites scored higher for quality than accuracy. Website usability and accuracy in a crisis situation were also assessed. The median crisis usability score was 3 out of five, and the median crisis accuracy score was 3.5 out of five. CONCLUSIONS: The inaccurate and inconsistent burn first aid treatments that appear online are reflected in the often-incorrect burn first aid treatments seen in patients attending emergency departments. Global consistency in burn first aid information is needed to avoid confusion by members of the public.

In Vivo Pig-a gene mutation assay: Guidance for 3Rs-friendly implementation.

The rodent Pig-a assay is an in vivo method for the detection of gene mutation, where lack of glycosylphosphatidylinositol-anchored proteins on the surface of circulating red blood cells (RBCs) serves as a reporter for Pig-a gene mutation. In the case of rats, the frequency of mutant phenotype RBCs is measured via fluorescent anti-CD59 antibodies and flow cytometry. The Pig-a assay meets the growing expectations for novel approaches in animal experimentation not only focusing on the scientific value of the assay but also on animal welfare aspects (3Rs principles), for example, amenable to integration into pivotal rodent 28-day general toxicology studies. However, as recommended in the Organisation for Economic Co-operation and Development Test Guidelines for genotoxicity testing, laboratories are expected to demonstrate their proficiency. While this has historically involved the extensive use of animals, here we describe an alternative approach based on a series of blood dilutions covering a range of mutant frequencies. The experiments described herein utilized either non-fluorescent anti-CD59 antibodies to provide elevated numbers of mutant-like cells, or a low volume blood sample from a single N-ethyl-N-nitrosourea treated animal. Results from these so-called reconstruction experiments from four independent laboratories showed good overall precision (correlation coefficients: 0.9979-0.9999) and accuracy (estimated slope: 0.71-1.09) of mutant cell scoring, which was further confirmed by Bland-Altman analysis. These data strongly support the use of reconstruction experiments for training purposes and demonstrating laboratory proficiency with very few animals, an ideal situation given the typically conflicting goals of demonstrating laboratory proficiency and reducing the use of animals. Environ. Mol. Mutagen. 57:678-686, 2016. © 2016 Wiley Periodicals, Inc.

Trypsin-resistant forms of human growth hormone have diabetogenic and insulin-like activities.

Although diabetogenic and insulin-like activities are intrinsic properties of the growth hormone (GH) molecule, it has been frequently suggested that the hormone must be proteolytically processed for these activities to be expressed. If this is correct, then derivatives of GH having resistance to appropriate proteolytic attack might not have diabetogenic and/or insulin-like activity. The purpose of the present study was to prepare derivatives of human GH that are resistant to digestion by trypsin and to determine whether they possess diabetogenic or insulin-like activity. Three derivatives were prepared from purified native human GH in which lysine residues were modified with methyl acetimidate, citraconic anhydride or S-ethyl-thioltrifluoroacetate, and one in which arginine residues were modified with camphorquinone-10-sulfonic acid. Comparisons of peptide maps of tryptic digests of these derivatives with that of unmodified human GH indicated that all four were resistant to proteolysis by trypsin. All of these trypsin-resistant forms of human GH were found to possess significant growth-promoting, diabetogenic and insulin-like activities, although all activities were attenuated to some extent in each derivative. The relative potencies of the human GH derivatives in a radioimmunoassay for human GH were somewhat similar to their order of potency in the growth-promoting and diabetogenic assays. These results suggest that if proteolytic processing of the GH molecule is involved in the expression of one or more of its biological activities, such processing probably does not involve a trypsin-like proteinase.

Biological characterization of purified native 20-kDa human growth hormone.

Because of the propensity of the 20-kDa variant of human growth hormone (GH) to aggregate with itself and with 22-kDa human GH, it has been difficult to prepare monomeric 20-kDa GH in highly purified form. This has been a major complicating factor in determining whether 20-kDa GH has a biological activity profile distinct from that of 22-kDa GH. In the present study, native 20-kDa GH was isolated from a human GH dimer concentrate and purified by a procedure that included column electrophoresis in agarose suspension as a final separation step. This procedure yielded highly purified monomeric 20-kDa GH, which was contaminated to an extent of less than 1% with 22-kDa GH, and which exhibited only a small degree of dimerization upon storage. The native 20-kDa GH was quite active in stimulating growth in hypophysectomized rats, when growth was assessed by body weight gain, longitudinal bone growth, the stimulation of sulfation of cartilage, and the elevation of serum IGF-1 level. However, in all of these growth assays, the 20-kDa GH was somewhat less active than the native 22-kDa GH to which it was compared; e.g., in the body weight gain and longitudinal bone growth assays, it had an estimated potency of 0.6 relative to the 22-kDa GH. The 20-kDa GH exhibited substantial diabetogenic activity when tested for the ability to raise fasting blood glucose concentration and to impair glucose tolerance in ob/ob mice. Also, the native 20-kDa GH had significant in vitro insulin-like activity, although its potency was approximately 20% that of the native 22-kDa GH to which it was compared. Thus, the biological activity profile of native 20-kDa GH differs from that of 22-kDa GH primarily in that insulin-like activity is markedly attenuated.

Influence of age on responsiveness to diabetogenic action of growth hormone.

Responsiveness to the growth-promoting action of growth hormone (GH) develops gradually during post-natal life, and as the organism ages, sensitivity to the hormone declines. Our study was undertaken to determine whether there is a similar age-related pattern of sensitivity to the diabetogenic action of purified native human GH (hGH) in the obese (ob/ob) mouse. The ob/ob mouse was used because adults of this strain respond to chronic GH treatment with increases in fasting plasma insulin and blood glucose concentrations and with glucose intolerance. When hGH was given subcutaneously to adult (4-mo-old) female mice at doses of 5, 10, or 25 micrograms/day for 3 days, a significant increase in fasting blood glucose concentration and an impairment in glucose tolerance were produced by the 10-micrograms/day dose. Larger effects were obtained with the 25-micrograms/day dose. A threefold increase in fasting plasma insulin concentration was also produced with this dose of the hormone. By contrast, 25 micrograms/day of hGH had no effect on fasting plasma insulin, blood glucose, or glucose tolerance in 1-mo-old ob/ob mice. When a dose of 100 micrograms/day of hGH was given to 1-mo-old animals, a significant increase in fasting plasma insulin concentration occurred, but again there were no effects on fasting blood glucose or glucose tolerance. Mice 1.5 mo old showed marginal changes in fasting blood glucose and glucose tolerance when given hGH at doses of 25 or 100 micrograms/day. Mice 9 or 12 mo old exhibited responsiveness similar to that of 4-mo-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Indicators of injury burden: which types are the most important?

Injury indicators are used for monitoring the impact of injury prevention initiatives on the population burden of injury. The object of the present study was to identify the types of injury responsible for the major component of the population health burden of injury in a large cohort in Manitoba, Canada. Injury cases (ICD-9-CM 800-995) aged 18-64 years were identified from all Manitoba hospital data between 1988 and 1991. Morbidity data were obtained from hospital discharge abstracts 12 months prior to date of injury and for 12 months post-injury. Outcomes for individuals were calculated as the difference pre- and post-injury in hospital inpatient days. Death outcomes in the 12 months post-injury were obtained by linking the cohort with the population registry. Summed outcomes across the population were stratified into injury types based on the International Code of Diseases (ICD) code of the index injury. Outcomes were also stratified by injury severity score categories where the injury severity score was obtained using ICDMAP-90. When ranked by contribution to the cohort's cumulative hospital inpatient days in the 12 months post-injury, the six most common ICD subchapter groups accounted for 65% of the total inpatient days. These six injury types also accounted for 62% of the total number of deaths in this cohort in 12 months after injury. The suggested injury types to use as indicators of burden include fracture of the lower limb, fracture of the head and neck, poisonings, intracranial injury, fracture of the upper limb, and fracture of skull.

How well do anatomical-based injury severity scores predict health service use in the 12 months after injury?

There is an acknowledged need for valid and reliable injury scores, suitable for use at the population level, which can accurately predict the long-term outcome of injury. The objective was to quantify the extent to which the abbreviated injury severity score (AIS) and the functional capacity index score (FCI) predict use of health services in the 12 months following an injury event. A cohort of injured people (ICD-9-CM 800-995) aged 18 - 64 years was identified from Manitoba hospital discharge abstracts from January 1988 to December 1991. For each member of the cohort whose injuries could be mapped to an abbreviated injury scale unique identifier, a maximum AIS (maxAIS) and a maximum FCI (maxFCI) were obtained. The cohort was linked with hospital discharge abstracts, physicians' claims and deaths from the population registry for the 12 months following injury. Negative binomial regression was used to model the relationships between the severity scores and the three outcome measures, while controlling for potential confounding variables. In total, 20 677 (97%) eligible cases were identified, of which 16 834 (81%) could be assigned a maxAIS and 15 823 (77%) a maxFCI. MaxAIS and maxFCI were significantly associated with total days in hospital following injury, but explained little of the variation in any of the health service use outcome variables (maxAIS, partial pseudo r2 ranging from < 0.001 to 0.041; and maxFCI, partial pseudo r2 ranging from < 0.001 to 0.018). It was concluded that anatomical damage is only partly responsible for long-term injury outcome. Additional variables would need to be included in predictive models of health outcomes of injury before these models could be reliable.

Case series of four-factor prothrombin complex concentrate for warfarin reversal before heart transplantation.

OBJECTIVE: Describe the experience of using 4-factor prothrombin complex concentrate (PCC4) in patients with a ventricular assist device (VAD) scheduled for imminent heart transplant who are receiving warfarin. METHODS: We are reporting a clinical case series describing 4 patients with VADs treated with PCC4 for anticoagulation reversal before heart transplantation. Data collection was performed via retrospective medical chart review from March 27, 2014, to July 20, 2014. RESULTS: Average time to anticoagulation reversal was 2.45 hours and average volume of PCC4 injection was 86 mL. No patient experienced a thromboembolic event or a decrease in hemoglobin indicative of a bleeding event. Average volume of packed red blood cells, platelets, and fresh frozen plasma (FFP) patients received was 2,325 mL. Patient 1 experienced a hypersensitivity reaction and patient 2 experienced thrombocytopenia postoperatively. The average acquisition cost was $3,824 and the average retail price was $7,143 per complete dose. CONCLUSIONS: PCC4 contributed to efficient reduction of International Normalized Ratio (INR) before surgery. PCC4 requires less volume than FFP for similar INR reductions. PCC4 was a beneficial agent in our patients with VADs; however, a cost-benefit analysis is needed to evaluate the future utility of PCC4.

Extracellular calcium ion concentration required for prolactin to express its actions on casein, ribonucleic acid, and lipid biosynthesis in mouse mammary gland explants.

The depletion of extracellular calcium ions by EGTA abolishes the PRL stimulation of [14C]acetate incorporation into lipids in mouse mammary gland explants. This abolition is reversed by the addition of calcium, but not magnesium. The chelation of calcium ions was similarly shown in earlier studies to abolish PRL's actions on RNA and casein synthesis. When the actions of PRL on lipid, RNA, and casein biosynthesis were tested when the extracellular calcium ion concentration was varied, it was observed that 5-10 microM calcium was required for PRL to manifest its actions. The calcium ionophore A23187 was unable, however, to mimic the PRL stimulation of lipid, RNA, or casein synthesis. Trifluoperazine, an inhibitor of calmodulin action had no effect on the PRL-induced synthesis of lipids, RNA, or casein, except at pharmacological levels.